Prostaglandins D2 and E2 have opposite effects on alveolar macrophages infected with Histoplasma capsulatum

Abstract

Prostaglandin E (PGE) suppresses macrophage effector mechanisms; however, little is known about the function of PGD in infected alveolar macrophages (AMs). Using serum-opsonized (Ops-) in vitro, we demonstrated that AMs produced PGE and PGD in a time-dependent manner, with PGE levels exceeding those of PGD by 48 h postinfection. Comparison of the effects of both exogenous PGs on AMs revealed that PGD increased phagocytosis and killing through the chemoattractant receptor-homologous molecule expressed on Th2 lymphocytes receptor, whereas PGE had opposite effects, through E prostanoid (EP) receptor 2 (EP2)/EP4-dependent mechanisms. Moreover, PGD inhibited phospholipase C-γ (PLC-γ) phosphorylation, reduced IL-10 production, and increased leukotriene B4 receptor expression. In contrast, exogenous PGE treatment reduced PLC-γ phosphorylation, p38 and nuclear factor κB activation, TNF-α, HO, and leukotriene B, but increased IL-1β production. Using specific compounds to inhibit the synthesis of each PG in vitro and in vivo, we found that endogenous PGD contributed to fungicidal mechanisms and controlled inflammation, whereas endogenous PGE decreased phagocytosis and killing of the fungus and induced inflammation. These findings demonstrate that, although PGD acts as an immunostimulatory mediator to control infection, PGE has immunosuppressive effects, and the balance between these two PGs may limit collateral immune damage at the expense of microbial containment.

Prostaglandin D2 synthase modulates macrophage activity and accumulation in injured peripheral nerves

“…Despite the increased number of macrophages, we observed accumulation of degenerated fibers in T14 L ‐ pgds −/− nerves. Notably, we demonstrate that L‐PGDS promotes macrophage activity similarly to previous works showing that treatment of infected alveolar macrophages with PGD 2 increases macrophage phagocytosis (Pereira et al, ). Thus, although in L ‐ pgds −/− nerves macrophages are less active and myelin clearance is delayed, their accumulation at T14 likely compensates for their reduced phagocytic activity.…”

Prostaglandin E2 Induces Expression of Mineralization Genes by Undifferentiated Dental Pulp Cells

“…That might be explained by the fact that eicosanoid encapsulation preserves the biological activity of lipid mediators by preventing their degradation (9). In fact, PGE 2 have been effectively encapsulated in PLGA with no loss of biological activity, because lactic/glycolic acid polymers show high encapsulation efficiency and adequate stability (10). A similar method for loading of PGE 2 showed that peak levels were reached in the first 4 h, but it could also be released continuously over longer periods (11).…”

“…One shortcoming is that PGE 2 shows a half-life relatively short. Therefore to preserve its biological activities and protect the mediator from degradation, loading of lipid mediators in microspheres has been used as a pharmacological strategy (9,10). However, the role of lipid mediator, loaded in microspheres or are not, in dental pulp cell differentiation is not clear.…”

Inhibition of Osteoclast Differentiation and Activation by Leukotriene B4 Loaded in Microspheres

“…Lipid mediators derived from arachidonic acid are widely studied in inflammation and inflammatory cell differentiation (Secatto et al, 2014;Zoccal et al, 2016;Prado et al, 2017;Pereira et al, 2018). However, the role of these mediators in osteoclast precursor cell populations present at the inflammation site is poorly understood.…”